An active-control trial of lamotrigine monotherapy for partial seizures

OBJECTIVE: We report the results of a double-blind, double-dummy, active-control study designed to evaluate the efficacy and safety of lamotrigine (LTG) administered as monotherapy to adult outpatients with partial seizures. BACKGROUND: The effectiveness of LTG as add-on therapy for partial seizures in adults has previously been established. METHODS: After an 8-week baseline during which patients continued their baseline antiepileptic drug (carbamazepine or phenytoin monotherapy), 156 patients were randomly assigned to receive increasing doses of LTG (target 250 mg b.i.d.) or valproic acid (VPA; target low dose of 500 mg b.i.d.) during the first 4 weeks of an 8-week transition period. Carbamazepine or phenytoin was withdrawn over the next 4 weeks; then patients entered a 12-week monotherapy period. Study drug treatment was discontinued in patients who met predetermined escape criteria for seizure worsening. RESULTS: More patients receiving LTG were successfully maintained on monotherapy compared with patients receiving VPA (56% versus 20%; p < 0.001). The time to meet the escape criteria was also significantly longer in LTG-treated patients (median = 168 days) than in VPA-treated patients (median = 57 days; p = 0.001). The incidence of adverse events during the monotherapy period was lower than during the transition period. Four LTG patients and five VPA patients reported serious adverse events. Two of those patients experienced a rash that led to withdrawal soon after adding LTG to carbamazepine. CONCLUSIONS: We conclude that LTG is effective and well tolerated when administered as monotherapy in adult patients with partial seizures.     

Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group

An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.     

A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group

Noninvasive alternatives to esophageal pressure (Pes) are needed to evaluate respiratory effort during sleep. Pulse transit time (PTT) is the time taken for pulse pressure to travel from the aortic valve to the periphery. PTT has been shown to be inversely correlated with blood pressure, and can reveal acute changes generated by high pleural pressure swings during pulsus paradoxus. A close relationship has been demonstrated between the increase in Pes and a progressive rise in the amplitude of PTT oscillations. The aim of the present study was to assess the accuracy of PTT for the classification of sleep respiratory events as central or obstructive. Respiratory events occurring during sleep were randomly chosen from 13 unselected male patients (mean apnea-hypopnea index [AHI] = 25.1 per hour of sleep; age = 47.3 yr, body mass index [BMI] = 27.1 kg/m2). Two observers experienced in polysomnography classified 177 events on the basis of the "gold standard method": the measurement of Pes. For 167 events about which the observers agreed, the PTT signal was analyzed visually and independently by the two observers blinded to Pes, in order to reclassify the same sleep respiratory events. The two observers were in agreement for 94.6% of the events scored visually on PTT recordings. We evaluated sensitivity (Se) (Observer 1: 94%, Observer 2: 91%), specificity (Sp) (97% and 95%, respectively), negative predictive value (NPV) (95% and 92%, respectively), and positive predictive value (PPV) (96% and 94%, respectively), of PTT with Pes as the reference. Misclassifications of respiratory episodes were usually due to artifacts or baseline variations of the PTT signal (57%), and occurred during rapid eye movement (REM) sleep (42.8%). PTT has shown a high sensitivity and specificity in differentiating obstructive and central respiratory events, and may become the reference noninvasive tool for this purpose.     

Chemotherapy without irradiation--a novel approach for newly diagnosed CNS germ cell tumors: results of an international cooperative trial. The First International Central Nervous System Germ Cell Tumor Study

PURPOSE: Radiation therapy for CNS germ cell tumors (GCT) is commonly associated with neurologic sequelae. We designed a therapeutic trial to determine whether irradiation could be avoided. PATIENTS AND METHODS: Patients received four cycles of carboplatin, etoposide, and bleomycin. Those with a complete response (CR) received two further cycles; others received two cycles intensified by cyclophosphamide. RESULTS: Seventy-one patients were enrolled (45 with germinoma and 26 with nongerminomatous GCT [NGGCT]). Sixty-eight were assessable for response. Thirty-nine of 68 (57%) achieved a CR within four cycles. Of 29 patients with less than a CR, 16 achieved CR with intensified chemotherapy or second surgery. Overall, 55 of 71 (78%) achieved a CR without irradiation. The CR rate was 84% for germinomas and 78% for NGGCT. With a median follow-up duration of 31 months, 28 of 71 patients were alive without relapse or progression. Thirty-five showed tumor recurrence (n = 28) or progression (n = 7) at a median of 13 months. Twenty-six of 28 patients (93%) who recurred following remission underwent successful salvage therapy. Pathology was the only variable predictive of survival. The probability of surviving 2 years was .84 for germinoma patients and .62 for NGGCT. Seven of 71 patients died of toxicity associated with study chemotherapy. CONCLUSION: Forty-one percent of surviving patients and 50% of all patients were treated successfully with chemotherapy only without irradiation. Chemotherapy-only regimens for CNS GCT, although encouraging, should continue to be used only in the setting of formal clinical trials.     

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group

OBJECTIVE: To examine the outcome of trial second labor after a first cesarean performed because of cephalopelvic disproportion, defined according to strict diagnostic criteria. METHODS: Obstetric details of nulliparous women delivering at 37 or more weeks' gestation by cesarean for cephalopelvic disproportion, between 1975 and 1990, were recorded prospectively. The diagnostic criteria for cephalopelvic disproportion were cervical dilation arrested after 5 cm, unresponsive to oxytocin augmentation, after active dilatation of 2 cm or more in 2 hours. Fetal malpresentations and malpositions were excluded. The outcome of next delivery in our hospital by each woman enrolled was then examined. RESULTS: Eighty-four of 42,793 women met the criteria for disproportion, and 40 with cephalic presentations delivered their next baby in our hospital. All 40 underwent a trial of labor and 27 (68%) delivered vaginally, comprising seven (47%) women with larger second and 20 (80%) with smaller second babies. Of 15 women previously delivered by cesarean at full dilatation, 11 (73%) delivered vaginally with no serious maternal or neonatal morbidity. CONCLUSION: The strictly defined diagnosis of nulliparous cephalopelvic disproportion should not constitute an automatic "recurrent" indication for elective cesarean delivery, because 68% of patients in our series had successful vaginal deliveries in their next pregnancies. This rate is similar to those reported after all nulliparous cesareans for dystocia.     

A multicenter trial of ropinirole as adjunct treatment for Parkinson's disease. Ropinirole Study Group

OBJECTIVE: To evaluate the nonergot dopamine agonist ropinirole as an adjunct to L-dopa in a randomized, double-blind trial in PD patients with motor fluctuations. BACKGROUND: L-dopa in the treatment of PD is associated with motor fluctuations, dyskinesia, and other adverse effects. The use of dopamine agonists in the treatment of PD delays recourse to L-dopa and thus delays the possibility of adverse effect onset. METHODS: Ropinirole (n = 95) or placebo (n = 54) was added to L-dopa, and L-dopa was then reduced in a planned manner during the 6-month trial. RESULTS: A significantly greater number of ropinirole patients were able to achieve a 20% or greater reduction in both L-dopa dose and in percent time spent "off" compared with placebo (35.0% versus 13.0%; p = 0.003). The mean daily L-dopa dose was reduced significantly with ropinirole treatment (242 mg versus 51 mg; p < 0.001) as was the percent awake time spent "off" (11.7% versus 5.1%; p = 0.039). There was no difference in the percent of patients who withdrew because of adverse effects (15.8% on ropinirole versus 16.7% on placebo). CONCLUSIONS: Ropinirole permits a reduction in L-dopa dose with enhanced clinical benefit for PD patients with motor fluctuations.     

A randomized trial in patients inadequately controlled with timolol alone comparing the dorzolamide-timolol combination to monotherapy with timolol or dorzolamide. Dorzolamide-Timolol Combination Study Group

OBJECTIVE: To compare the dorzolamide-timolol fixed combination twice daily to its components, timolol maleate and dorzolamide hydrochloride, given in their usual monotherapy regimens in patients whose intraocular pressure (IOP) was not controlled on timolol twice daily alone. DESIGN: Parallel, randomized, double-masked, and active-controlled study. PARTICIPANTS: Enrolled were 253 patients from 22 sites throughout the United States. INTERVENTION: After a 3-week run-in of timolol (TIMOPTIC; Merck & Co., Inc., Whitehouse Station, NJ) twice daily, eligible patients received either the combination (COSOPT; Merck & Co., Inc., Whitehouse Station, NJ) twice daily (plus placebo to ensure masking), timolol twice daily (plus placebo to ensure masking), or dorzolamide (TRUSOPT; Merck & Co. Inc., Whitehouse Station, NJ) three times daily for 3 months. MAIN OUTCOME MEASURES: Intraocular pressure taken at hours 0 (trough) and 2 (peak) after week 2 and months 1, 2, and 3 was compared to baseline within each treatment group and between the combination and each component group. The safety profile of the combination was compared to each component. RESULTS: The combination was numerically superior at all study timepoints and was statistically superior at all timepoints except for month 2, hour 0 for timolol, and month 2, hour 2 for dorzolamide. The safety profile of the combination reflected those of its two components. The number of patients reporting ocular or local adverse experiences was greater for the combination (45%) and dorzolamide (45%) than for timolol (27%), with burning and/or stinging eye being the most frequently reported. CONCLUSION: The dorzolamide-timolol combination provides additional IOP lowering compared to either of its individual components and generally is well-tolerated.     

Randomized comparison of intravenous immunoglobulin and methylprednisolone pulse therapy in children with newly diagnosed idiopathic thrombocytic purpura. The Danish ITP Study Group

Forty three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (pl.c.) below 20 x 10(9)/l, and either clinically significant bleeding or failure to show a spontaneous platelet rise within three days of admission were randomly allocated to treatment with intravenous infusions of either immunoglobulin (IVIG) 1 g/kg or methylprednisolone (MPPT) 30 mg/kg on two consecutive days. Prompt induction of partial remission with pl.c. > 50 x 10(9)/l after 72 hours was seen in 21/23 given IVIG versus 10/20 given MPPT (exact p = 0.003); mean pl.c.s after 72 hours were 188 versus 77 x 10(9)/l (2p < 0.001). Poor responders were then given the alternative infusions in addition. After six days, complete remission with pl.c. > 150 x 10(9)/l was achieved in 16/23 versus 10/20 (p = 0.16). During six months follow-up, there were no significant differences regarding relapse rates or chronic course. Eleven children with relapse were crossed over to the alternative treatment arm: the estimated treatment effect in pl.c. after 72 hours was 134 x 10(9)/l in favour of IVIG. These results indicate that IVIG infusions may be preferable to high-dose corticosteroids as initial treatment for children with ITP.     

Salmeterol compared with slow-release terbutaline in nocturnal asthma. A multicenter, randomized, double-blind, double-dummy, sequential clinical trial. French Multicenter Study Group

The aim of the multicenter, randomized, double-blind, double-dummy, parallel-group clinical trial with a 2-week treatment period was to compare the efficacy and safety of salmeterol (50 micrograms twice daily) with slow-release (SR) terbutaline (5 mg orally, twice daily) in nocturnal asthma. A total of 159 asthmatic adults (FEV, 50-90% of predicted value; sex ratio: 0.87) with at least two nocturnal awakenings during a 7-d run-in period was included in the study. Patients were centrally randomized with a national computer network (Minitel). The main variable (number of awakening-free nights during the last week of treatment) was analyzed according to a sequential method with the one-sided triangular test. The number of awakening-free nights (+/- SD) was significantly higher in the salmeterol group: 5.3 +/- 2.4 vs 4.6 +/- 2.3 (P = 0.006). Salmeterol was significantly more effective than SR-terbutaline in the following factors: number of patients without any awakening during the last week of treatment (50% vs 27%, P = 0.003), mean morning PEF (351 +/- 109 l/min-1 vs 332 +/- 105 l/min-1, P = 0.04), PEF diurnal variation 6 +/- 10% vs 11 +/- 12%, P = 0.01), overall assessment of efficacy by the patient and the investigator (P = 0.001 and 0.005, respectively), and daily rescue salbutamol intakes (P = 0.004). In the salmeterol group, significantly fewer patients reported adverse events (16% vs 29%, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized, double-blind clinical trial comparing cefepime plus metronidazole with imipenem-cilastatin in the treatment of complicated intra-abdominal infections. Cefepime Intra-abdominal Infection Study Group

OBJECTIVE: To evaluate the safety and efficacy of cefepime hydrochloride plus metronidazole vs the combination of imipenem and cilastatin sodium in the treatment of complicated intra-abdominal infections in adult patients. DESIGN: Prospective, randomized, double-blind multicenter study. SETTING: University-affiliated hospitals in the United States and Canada. PATIENTS: Three hundred twenty-three patients with complicated intra-abdominal infections in whom an operative procedure or percutaneous drainage was required for diagnosis and management. INTERVENTION: Cefepime, 2 g, was administered intravenously every 12 hours (n= 164) in addition to metronidazole, 500 mg (or 7.5 mg/kg) intravenously every 6 hours. Imipenen-cilastatin sodium, 500 mg, was administered intravenously every 6 hours (n= 159). Surgical infection management was determined by the patients' surgeons. MAIN OUTCOME ASSESSMENTS: Clinical cure, defined as elimination of all signs and symptoms relevant to the original infection; and treatment failure, defined as persistence, increase or worsening of signs and symptoms resulting in an antibiotic change, requirement of an additional surgical procedure to cure the infection, or a wound infection with fever. RESULTS: Of the initial isolates, 84% were susceptible to cefepime and 92% were susceptible to imipenem-cilastatin. Among the 217 protocol-valid patients, those treated with cefepime+metronidizole were deemed clinical cures (88%) more frequently than were imipenem-cilastatin-treated patients (76%) (P=.02). Using multivariate analysis to adjust for identified clinical risk factors for an adverse outcome (severity of presenting illness, isolation of enterococcus, type of infection, and duration of prestudy hospitalization), there was a trend (P=.06) toward a higher cure rate favoring cefepime+metronidazole. Pathogens were eradicated in significantly (P=.01) more patients treated with combined cefepime and metronidazole (89%) than with imipenem-cilastatin (76%). CONCLUSION: The combination of cefepime plus metronidazole is safe and effective therapy for patients with severe intra-abdominal infections.     

Glimepiride, a new once-daily sulfonylurea. A double-blind placebo-controlled study of NIDDM patients. Glimepiride Study Group

OBJECTIVE: To compare the efficacy and safety of two daily doses of the new sulfonylurea, glimepiride (Amaryl), each as a once-daily dose or in two divided doses, in patients with NIDDM. RESEARCH DESIGN AND METHODS: Of the previously treated NIDDM patients, 416 entered this multicenter randomized double-blind placebo-controlled fixed-dose study. After a 3-week placebo washout, patients received a 14-week course of placebo or glimepiride 8 mg q.d., 4 mg b.i.d., 16 mg q.d., or 8 mg b.i.d. RESULTS: Fasting plasma glucose (FPG) and HbA1c values were similar at baseline in all treatment groups. The placebo group's FPG value increased from 13.0 mmol/l at baseline to 14.5 mmol/l at the last evaluation endpoint (P < or = 0.001). In contrast, FPG values in the four glimepiride groups decreased from a range of 12.4-12.9 mmol/l at baseline to a range of 8.6-9.8 mmol/l at endpoint (P < or = 0.001, within-group change from baseline; P < or = 0.001, between-group change [vs. placebo] from baseline). Two-hour postprandial plasma glucose (PPG) findings were consistent with FPG findings. In the placebo group, the HbA1c value increased from 7.7% at baseline to 9.7% at endpoint (P < or = 0.001), whereas HbA1c values for the glimepiride groups were 7.9-8.1% at baseline and 7.4-7.6% at endpoint (P < or = 0.001, within-group change from baseline; P < or = 0.001, between-group change from baseline). There were no meaningful differences in glycemic variables between daily doses of 8 and 16 mg or between once- and twice-daily dosing. Adverse events and laboratory data demonstrate that glimepiride has a favorable safety profile. CONCLUSIONS: Glimepiride is an effective and well-tolerated oral glucose-lowering agent. The results of this study demonstrate maximum effectiveness can be achieved with 8 mg q.d. of glimepiride in NIDDM subjects.     

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group

BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients. METHODS: 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study. FINDINGS: 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group. INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.     

A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group

BACKGROUND: People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer. METHODS: We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo; beta carotene (25 mg daily); vitamin C (1 g daily) and vitamin E (400 mg daily); or the beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations. RESULTS: Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location. CONCLUSIONS: The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.     

A multicenter trial of photorefractive keratectomy for residual myopia after previous ocular surgery. Summit Therapeutic Refractive Study Group

PURPOSE: The Summit Therapeutic Refractive Clinical Trial is a nine-center prospective, nonrandomized, self-controlled trial to assess the efficacy, stability, and safety of using a standardized technique of excimer laser photorefractive keratectomy (PRK) to correct residual myopia in eyes with previous refractive surgery or cataract surgery. PATIENTS AND METHODS: Eligible eyes with a mean residual myopia of -3.7 +/- 1.8 diopters (D) (range, -0.63 to -11.00 D) underwent PRK with a 193-nm excimer laser for myopic corrections between -1.50 and -7.50 D. Standardized settings were used for the ablation zone, ablation rate, repetition rate, and fluence. One hundred seven of the first 114 treated eyes were examined 1 year after PRK, with 98% of eyes having had refractive keratotomy and 2% having had cataract surgery. RESULTS: One year postoperatively, the mean manifest spherical equivalent refraction was -0.6 +/- 1.4 D (range, -6.50 to 2.50 D); 63% of eyes were within +/-1.00 D of the attempted correction; and uncorrected visual acuity was 20/40 or better in 74% of eyes. Twenty-nine percent of eyes lost two or more Snellen lines of best-corrected visual acuity, and central corneal haze was moderate or severe in 8% of eyes. CONCLUSIONS: Excimer laser PRK is effective in reducing residual myopia after previous refractive and cataract surgery. However, it is less accurate than PRK in eyes that did not undergo surgery and is more likely to cause a loss of best-corrected visual acuity 1 year after treatment.     

Albendazole therapy for neurocysticercosis: a prospective double-blind trial comparing 7 versus 14 days of treatment. Cysticercosis Working Group in Peru

OBJECTIVE: To compare the effectiveness of two regimens of albendazole therapy for neurocysticercosis. DESIGN: Randomized, double-blind clinical trial. SETTINGS: Patients admitted to neurologic wards in Lima, Peru. PATIENTS: Adult patients with active neurocysticercosis demonstrated by CT and Western blot (immunoblot). INTERVENTION: One week (n = 25) versus 2 weeks (n = 25) of albendazole therapy. MEASUREMENTS: Decrease in the number of cysts on CT. RESULTS: Effectiveness of albendazole was 78%, with no difference between the groups when compared 3 months after therapy. Complete cure was obtained in only 38% of patients. Patients with more than 20 cysts had poorer responses to therapy. The clinical course and EEG evolution improved in most patients. Side effects were present in 38% of patients, mainly mild, transient gastrointestinal symptoms. Therapy was also associated with exacerbation of neurologic symptoms. Two patients died in the first year after therapy, both because of aggregated infections of ventricle-peritoneal shunts. One-year follow-up CT showed lesions in three of 10 patients presumed to be cured 3 months after therapy. CONCLUSIONS: Extension of albendazole therapy for more than 7 days adds no benefits for the patients.     

How and for whom are decision aids effective? Long-term psychological outcome of a randomized controlled trial in women with newly diagnosed breast cancer.

Objective: The current study evaluates the long-term psychological impact of a decision aid intervention for surgical and systemic treatment in women with newly diagnosed breast cancer from a previous reported randomized, controlled trial (Vodermaier et al., 2009). Methods: Patients (n = 111) were randomized into usual care, or a 20-min decision aid intervention plus an information brochure prior to consultation planning with the senior physician. The retention rate at 1 year was 88%. Results: Linear mixed model analyses demonstrated that the intervention group experienced less decisional conflict (p = .047; d = .19), which was driven by perceptions of a more effective choice (p = .029; d = .20) over time. Subgroup analyses revealed that patients in the intervention group who participated in chemotherapy decision making showed better long-term body image outcomes (p = .009; d = .44), which were mediated by reduced depressive coping (p = .049). No effects emerged for anxiety and depressive symptoms, or for quality of life. Internal health locus of control moderated group effects on 'uncertainty with the decision' (p = .003). Conclusions: The study results provide novel evidence on the role of individual differences and the mechanisms behind decision aid effectiveness, and demonstrate the long-term impact of decision aid interventions on some indices of well-being. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group

When chaperonins GroEL and GroES are incubated under functional conditions in the presence of ATP (5 mM) and K+ (150 mM), GroEL-GroES complexes appear in the incubation mixture, that are either asymmetric (1:1 GroEL:GroES oligomer ratio) or symmetric (1:2 GroEL:GroES oligomer ratio). The percentage of symmetric complexes present is directly related to the [ATP]/[ADP] ratio and to the K+ concentration. Kinetic analysis shows that there is a cycle of formation and disappearance of symmetric complexes. A correlation between the presence of symmetric complexes in the incubation mixture and its rhodanese folding activity suggests some active role of these complexes in the protein folding process. Accordingly, under functional conditions, symmetric complexes are found to contain denatured rhodanese. These data suggest that binding of substrate inside the GroEL cavity takes place before the symmetric complex is formed.     

A prospective multicenter trial of excimer laser phototherapeutic keratectomy for corneal vision loss. The Summit Phototherapeutic Keratectomy Study Group

PURPOSE: The 193-nm argon fluoride excimer laser can remove corneal scars and smooth corneal irregularities, obviating corneal transplantation. We conducted a prospective multicenter trial of excimer laser phototherapeutic keratectomy for corneal vision loss as a basis for Food and Drug Administration premarket approval. METHODS: We treated 232 eyes of 211 patients with corneal vision loss. All had corneal pathology in the anterior 100 microns of the stroma. Mean postoperative follow-up was 10 +/- 8 months. The primary outcome variable was change in best spectacle-corrected visual acuity. RESULTS: At postoperative month 12, best spectacle-corrected visual acuity improved in 46 (45%) of 103 eyes and worsened in nine (9%) of 103 eyes by 2 or more Snellen lines. Best spectacle-corrected visual acuity improved by a mean of 1.6 +/- 2.8 Snellen lines (95% confidence interval, 1.1 to 2.1 lines). Every postoperative visit confirmed statistically significant improvement of mean best spectacle-corrected acuity. At month 12, treated eyes had a mean hyperopic shift in refraction of 0.87 diopter and a mean reduction in astigmatism of 0.36 diopter. Treatment appeared most effective in eyes with hereditary corneal dystrophies, Salzmann's nodular degeneration, and corneal scars, and least effective in eyes with calcific band keratopathy. Complications included recurrence of underlying pathology, corneal graft rejection, and bacterial keratitis. CONCLUSIONS: Argon fluoride excimer laser phototherapeutic keratectomy is effective, with relatively few complications, for treating vision loss from corneal opacification or irregularity. Efficacy, however, varies widely depending upon individual eyes and underlying diagnoses.     

Evaluation of 6 weeks treatment of terbinafine in tinea unguium in a double-blind trial comparing 6 and 12 weeks therapy. The Lagos V Study Group

OBJECTIVES: This study sought to characterize the postoperative prostate-specific antigen (PSA) doubling time and time to biochemical recurrence in patients who have failed radical prostatectomy. METHODS: Of 539 consecutive patients who underwent radical prostatectomy between 1984 and 1992, postoperative PSA levels in 80 initially became undetectable (less than 0.07 ng/mL) before eventually increasing, as evidenced by rising PSA levels above the residual cancer detection limit of the Tosoh AIA-600 immunoassay run in the ultrasensitive mode (i.e., 0.07 ng/mL or higher). The PSA doubling time and time to biochemical recurrence were calculated for each of the 80 patients and were correlated with the histopathologic variables from the operative specimen. RESULTS: Postoperative PSA doubling times were predicted by the extent of capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and tumor volume on univariate analysis and by capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and patient age on multivariate analysis. Times to recurrence were predicted by the presence of positive margins and percent Gleason grade 4 or 5 in both univariate and multivariate regression models. The PSA doubling time did not correlate with recurrence time. The median PSA doubling time for all patients was 284 days, and the median time to recurrence was 648 days. CONCLUSIONS: These results demonstrate that PSA doubling time and recurrence time are indicative of different biologic characteristics of recurrent prostate cancer: Doubling time appears to represent the aggressiveness of the original prostate cancer, whereas time to recurrence reflects the extent of residual postoperative disease. This information should aid in the selection of men who need greater vigilance during postoperative surveillance.